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OBJECTIVE: The authors compared treatment and outcomes for depressed primary care patients with and without comorbid medical conditions and assessed the impact of quality improvement programs for these patients. METHOD: The study group included 1,356 patients with major depression, dysthymia, or subthreshold depression from 46 managed primary care clinics. Clinics were randomly assigned depression treatment programs consisting of usual care for depression or one of two quality improvement programs for depression. The quality improvement programs included training experts and nurse specialists to provide education and assessment, plus access to nurse specialists for medication follow-up or access to psychotherapists. Outcomes were assessed at 6 and 12 months. RESULTS: At 6- and 12-month follow-up, the likelihood of having a probable depressive disorder was higher, but the rates of use of antidepressant medication and specialty counseling were similar, for depressed patients with comorbid medical disorders than for depressed patients who did not have comorbid medical disorders. Among the depressed patients with comorbid medical disorders, the combined quality improvement programs resulted in greater use of antidepressant medications and psychotherapy and lower rates of probable depressive disorders at both 6- and 12-month follow-up than did the usual care depression treatment program. CONCLUSIONS: Depressed patients with comorbid medical disorders tend to have similar rates of treatment but worse depression outcomes than depressed patients without comorbid medical illness. Quality improvement programs for depression can improve treatment rates and outcomes for depressed primary care patients with comorbid medical illness. The authors discuss the implications of these findings for clinical practice.